Social importance: Chagas disease and the sanitary movement of the 1910

Simone Petraglia Kropf

Casa de Oswaldo Cruz/Fiocruz.

Email: simonek@coc.fiocruz.br

Nísia Trindade Lima

Casa de Oswaldo Cruz/Fiocruz

E-mail: lima@coc.fiocruz.br

The movement for sanitation in Brazil, triggered during the First Republic (1899-1930), highlighted the poor health conditions as the main obstacle for the country to become civilized and effectively become a nation. Its origin and trajectory were directly related to the history of Chagas disease.

In October 1916, Carlos Chagas and the Brazilian delegation were received upon their return from a medical congress held in Buenos Aires, with great honors by the medical class of Rio de Janeiro. They served not only as a statement of recognition to those who had represented the national science abroad, but as an occasion to give visibility to the meaning that, from the early years after its discovery, American trypanosomiasis had taken on as an emblem of the nation’s illness.

At the Faculty of Medicine of Rio de Janeiro, in honor of its director, Aloísio de Castro, for participating in the meeting in Argentina, Miguel Pereira delivered a speech in which he stated: “Brazil is a vast hospital”. The words of the then president of the National Academy of Medicine echoed not only in the medical world, but strongly reflected in the broader intellectual and political debate about national identity.

In the context of World War I, the moment was one of great nationalist fervor, and issues such as racial, immigration, education, and military recruitment intersected with the prospect of identifying the country’s illnesses and chances of “regeneration”. Pereira made the sanitary conditions of the hinterlands the axis of his criticism “(our) political misfortunes and (our) administrative misery”, as well as the ufanist preaching of those who urged all Brazilians to engage in the defense of civic and patriotic values. Ironizing the speech of the deputy from Minas Gerais Carlos Peixoto, who stated that he was willing to personally summon the “sertanejos” of his state to serve the Brazilian Army, he said:

“It is good to organize militias, to arm legions, to close ranks around the flag, but it would be better if they did not forget in this paroxysm of the enthusiasm that, outside Rio or S. Paulo, more or less sanitized capitals, and from some other cities where providence oversees hygiene, Brazil is still a vast hospital. (…) In reaching such an extreme of patriotic zeal a great disappointment would welcome his generous and noble initiative. Part, and ponderal part, of these brave people would not rise; invalids, bloodless, depleted by hookworm and malaria; maimed and devastated by Chagas disease; corroded by syphilis and leprosy; (…) I do not carry colors to the board. This is, without exaggeration, our inland population. A legion of sick and worthless”. (“The Academic Manifestation to Professor Aloysio de Castro”, w.n., (October 1916), Chagas Family Fund, Carlos Chagas Papers, Newspaper Scrapbook).

The next day Miguel Pereira gave a new speech, this time at a banquet in honor of Chagas. Here his complaint about the sanitary calamity of the interior of the country appears as a corollary of the praise given to the discoverer of what stood out as one of the most serious causes of this “hecatomb”. Among the meanings behind this praise was that of displeasure, for the criticism that Chagas’ conceptions about the clinical characterisation and the epidemiological importance of trypanosomiasis had been receiving from researchers in Argentina.

In response to those who doubted the morbid entity, whose best-known name – parasitic thyroiditis – had been coined by himself, Pereira emphasized the social mission of the “men of science” who, like Chagas, went to the backlands and revealed the sad reality there. Unknown, abandoned, sick Brazil, which could only respond to patriotic claims through “an army of shadows” (“Banquet to Dr. Carlos Chagas” 1916).

Thanking the tribute, Chagas emphatically reiterated his colleague’s statements, which he described as “a magnificent panel of melancholic truths.” Defending him from those who condemned him as pessimistic or exaggerating the image of the country as a “vast hospital”, he presented his own testimony as a scholar of a disease that was, as he’s been saying since 1910, one of the greatest health problems in the interior of Brazil.

“I know very closely those harrowing aspects of country life, photographed in the master’s word. (…) As for the Brazilian trypanosomiasis, I have spoken to you many times, always with the aim of benefiting the vast areas of the interior of my country, devastated by the deadly disease. Do you doubt the black colors with which we describe its harms? We have very close the convenient documentation, which shows the greatest calamity of our backlands. ”

These two speeches by Miguel Pereira are considered by historiography as the origin mark of the so-called sanitation movement in Brazil. Between 1916 and 1920, this campaign brought together doctors, scientists, intellectuals, and politicians around the idea that Brazil’s backwardness to civilized nations was not the result of the tropical climate or racial makeup of its population, but due to the damage caused by endemics to the productivity of labor and the neglect of the state with the populations of the interior. This diagnosis – based, above all, on the reports of the researchers’ trips from Manguinhos to the interior, which updated Euclides da Cunha’s denunciation of the isolation and abandonment that marked the country’s hinterlands – was in opposition to the idyllic vision of the rural environment and its inhabitants advocated by the romantic literature and even by medical discourse.

As a political movement, it expressed itself fundamentally in the demand that the Brazilian State would increase its power of intervention in the field of public health. With great repercussions in the press, intellectuals and the National Congress, the movement, formally organized in the Pro-Sanitation League of Brazil (created in 1918 and directed by Belisário Penna), would lead to a broad reform of the health services, with the creation, in late 1919, the National Department of Public Health (DNSP), of which Chagas would be the first director.

The conception that diseases that raged in the backlands were the main obstacle to the economic and social progresses of the country the to the construction of nationality was defended by Carlos Chagas from 1910 onwards, while at the same time producing medical statements about American trypanosomiasis, framed it as a social problem, a “disease of Brazil,” representing the country’s problems and the science that he intended to solve. Pereira’s speech, therefore, should be considered a milestone not for inaugurating the notion of sick Brazil, but for giving it a new breadth, beyond the medical and scientific circles, making from it a concrete program of intervention and social reform.

The main documents disseminating the ideas of the movement for rural sanitation in the country had a decisive impact on the scientific and social trajectory of trypanosomiasis. If, on the one hand, in a context of scientific controversy, the clinical design of the disease was going through a new framework, in which the most prominent features (such as endocrine disorders) would be minimized by Chagas himself in 1916, on the other hand, the political movement that, starting this year, would project the disease into the national debate would reinforce, precisely, one of the main elements that Chagas sought to minimize: the goiter. In the sanitary discourse, it would remain the “seal of disease” (coined by Miguel Couto in 1910), representing, along with neurological disorders, the dramatic effects not only of American trypanosomiasis, but of the morbid condition of all who perished in the interior of the country.

A decisive vehicle for propagating this representation was the report of the celebrated scientific expedition by Arthur Neiva and Belisario Penna to the northeast and midwest of the country, published in 1916. In addition to their primary objective of mapping the nosological framework of the region, the trip produced a detailed inventory of the physical and social environment of an inhospitable and unknown region of “Central Brazil”, revealing a picture of disease, misery and absence of public power.

One of the goals of the 1912 trip was precisely to find evidence to support Chagas’s idea of the extensive geographical spread of American trypanosomiasis. Along the way, Neiva and Penna located different species of “barbers”, performing tests to see if they were infected with T. cruzi. The constant presence of barred houses with barred walls indicated epidemiological conditions propitious to the spread of the disease transmitted by those insects. Along with the “cafua” and “barbers”, the “goitre” – which, when the trip was made, was widely accepted as the main sign to suspect human cases of Chagas disease – was the prime criterion for identifying the presence of this disease.

In Goiás, Neiva and Penna found the largest amount of evidence of the “concomitant presence of goiter and triatomas in households”. The remarks about the “goitre” in the capital of Goiás – where this condition had disappeared with the modernization of the houses, but remained in the muddy dwellings of the suburbs – were an element to reinforce the idea that the housing of the “backward sertanejas villages” was the causal link between goiter and trypanosomiasis transmitters. This association corroborated the parasitic etiology of goiter proposed by Chagas, which the authors presented with reservation, as “hypothesis”.

Despite this caution, goitre was in fact used as the primary criterion for defining the presence of Chagas disease during the travel route. It is precisely in describing the places where it was identified by this sign – as in Goiás, where “flagella in proportions not even suspected of the Nation” – that Neiva and Pena extract from its “thyroiditis” all its implications as a major symbol of the physical and social degradation of the interior populations, devastated by rural endemics.

The photographs taken during the expedition, focusing on various physical and social aspects of the traveled regions, were a powerful persuasive resource in relation to the ideas that scientists intended to make, such as the abandonment and misery of the “sertanejos”. Of the 24 photographs of patients, 18 referred to Chagas disease, which was equally central to the textual description of pathologies. Firming, as Stepan points out, a certain way of seeing and recognizing the disease, practically all these images had in the “goitre” (which in some cases took on huge volumes and was accompanied by nervous disorders) the most salient feature. Such photographs, as they added to the Lassance’s portraits, faces from another region of the country, corroborated the scientists’ goal of demonstrating the widespread spread of the disease throughout the country.

With a repercussion that surpassed the borders of the medical field, in a context that echoed Miguel Pereira’s cry, the report was evoked as the documentary basis to legitimize the statements and claims of the campaign for sanitation in Brazil, which won the pages of newspapers and the congress hall.

In addition to the Neiva-Penna´s report, another important vehicle for disseminating the public image of Chagas disease as a banner of the campaign for rural sanitation was Belisário Penna’s articles, published between 1916 and 1917 in the Correio da Manhã, which would be combined in the book Saneamento do Brasil, published in 1918 as the basis for the founding, that same year, of the Pro-Sanitation League of Brazil. Also in 1918, as a collection of texts for the daily press, circulated the book Problema Vital, in which the writer Monteiro Lobato expressed his adherence to the sanitary idea, synthesizing it in the famous character of Jeca Tatu as an example of the impact of diseases on countrymen and the possibilities of their redemption.

In Saneamento do Brasil, Penna stated that the economic problem of the country lay in the “unavoidable need to cure the rural man, to instruct him, to fix him and to give him the means to feed properly so that he can produce a man with normal health”. This alert sounded particularly urgent for the state of Minas Gerais, where the subject of economic stagnation had been worrying the political elites and which, according to Penna himself, despite being the emblem of the “agricultural vocation of the country”, was unfortunately characterizing as the “disease state”, plagued by rural endemics, especially the disease discovered there by Carlos Chagas.

It was like the testimony of one who personally knew the reality of the interior of the country that Penna gave to the medical and social representation of Chagas disease, whose discovery he had witnessed in Lassance, a great persuasive and rhetorical force. In his descriptions, it was the “most fearful of the endemic scourges of the backlands,” for the physical and mental deformities it caused and the fact that it had no cure.

“Such a calamity is not limited to depressing the physical and moral of its victims, harming their essential organs of health and life; it deforms them to fantastic proportions, completely destroys them, forming legions of cripples, cretins, idiots, paralytics and “papuds” (…). This is the banal picture in the barber regions. Dr Neiva and I saw in the north of Goiás infernal pictures, which only the great Florentine poet could describe, creating some new cycle in his famous hell”.

The representation of trypanosomiasis as a “disease of Brazil” was made not only from the point of view of the diagnosis of the nation’s maladies, but also from the possibilities of overcoming them. He reiterated Chagas’ own statements, stating that the public authorities, through actions such as the improvement of rural dwellings, should intervene to solve the problems of the interior populations.

Referring to the clinical picture of the disease, despite claiming that the heart shape is “the most frequent”, Penna highlighted the endocrine and nervous disorders as more concrete traces of the impact of that disease that synthesized a complaint and a look at the nation. The inclusion of patient photographs in the book also helped to fix and highlight these traits. One of them focuses, in front and in profile, on the faces of two bearers of bulky “goiters”. The other has three individuals leaning against the mud wall of a “cafua”, with atrophied legs and arms and with a visible mental deficiency aspect. In a kind of general panel of the constitutive morbid picture of that entity, another photograph brings together sick people from Asylum S. Francisco, in Goiás, in which goiter and/or nervous disorders are easily identified.

Highlighting these elements, in turn, was fundamental to ensuring one of the main objectives that, having guided the 1912 expedition, was also present in Penna’s book: corroborating the notion that trypanosomiasis was a widespread disease in “a vast region of the Brazil”. Citing Chagas’ formulations in this respect in 1912, Penna emphasizes: “There is no exaggeration in these concepts that we saw Neiva and I, absolutely and widely confirmed in Goias. (…) There are locations (“arraiais”) where no one, literally, escapes the tremendous infection”. Without mentioning the origin of the estimate, he asserted that 15% of the national population would be affected by trypanosomiasis, or about three million Brazilians.

The thesis of the social impact of American trypanosomiasis would also be disseminated by Monteiro Lobato. In his book Problema Vital, published in 1918, Penna’s figures for the country’s sanitary “cataclysm” gained even more prominence, stamped in the titles of articles in which the writer addressed the “damn trinity” endemics: “seventeen million opilated ”,“ 10 million impaluded ”,“ 3 million idiots and “papudos” ”. Lobato reinstated Penna’s ideas about the general issue of sanitation as well as of trypanosomiasis. Under the literary verve, it gained even more vibrant colors as a metaphor for Brazil. Citing a passage from Saneamento do Brasil in which Penna reports the attack, witnessed in Lassance, of several “barbers” on one child, Lobato adds: “this child is not a child, but the child of the Brazilian backwoods…”. To synthesize the clinical procession of the disease, the writer proclaims, in a style that combines the tragic and the comic:

“Three million – three million! – of creatures bogged down in the most dismal mental and physiological misery by a cockroach’s arts! (…) Three million negative quantities, unable to produce, gnawing, hungry, the leftovers of others’ production – what is worse, condemned to the bad fate of lethal parasites nursery so that the abundance and permanent contamination of the healthy are well assured”.

Corroborating Penna’s acid criticism of politicians and literati’s indifference to the economic consequences of this “progressive demise of the population”, Lobato preaches the end of the power of the graduates – “triatoma bacalaureatus“, he says, comparing it in his “vampiric” action” to the “barber” himself – and his replacement, in the highest positions of the nation, by those who could in fact redeem it: the scientists. About Manguinhos, he said:

“Salvation is there. From there has come, come, and will come the saving truth – the scientific truth that comes out naked from the microscope field, as the ancient truth came out of the well”.

Also in 1918, Carlos Chagas published in Revista do Brasil, then owned by Lobato, an article in which he presented his general statements on American trypanosomiasis. The emphasis was on the most widespread aspect of Brazil’s sanitation campaign: the economic importance of rural prophylaxis. In a sentence that would be reproduced in several scientific articles and leaflets of the disease in the 1940s and 1950s (when the theme of prophylaxis would reach great projection), it stated:

“The fight against American trypanosomiasis represents, in our country, one of the most important health problems, linked to the highest economic interests and the progressive improvement of our race in rural areas”

If Brazilian doctors/scientists had, since the nineteenth century, gained public legitimacy through their commitment to answer questions considered of importance to society, at that time, they were not only recognized for their ability to point out such problems, but also for their concerns and aspirations to occupy a place with the state, from which, with autonomy, could, in fact, dictate the course of the nation.

On the other hand, Chagas’s and the American trypanosomiasis’s maximum projection in the field of politics, while expressing and generating recognition and legitimacy, imposed a greater susceptibility to criticism, controversy and tension. Thus, if on the one hand it framed the cry of the sanitarians, the “disease of Brazil” would become the center of an intense controversy that recovered the scientific questions debated in Argentina, but gave them new meanings and implications. The famous episode of the controversy at the Academia Nacional de Medicina, between 1922 and 1923, would decisively mark the trajectories of the disease and its discoverer. In it, the scientific dimension would be intertwined with the political content of the disease debate. Those who questioned Chagas disease as a scientific object and social problem challenged those who classified Brazil as a “vast hospital”.

In summary, we have excellent laboratory diagnostic methods, both in the acute phase (direct examination, concentration methods) and in the chronic phase (conventional serological tests) that allow accurate diagnosis in more than 95% of cases. The latter are marketed and have been evaluated on different occasions. There is external quality control, to which most of the country’s blood banks are subjected. There are manuals for better technical performance. The rare cases of inconclusive serological results can be clarified by specialized laboratories. In emergencies, rapid tests, also available, may be used. It is expected soon to have commercially available PCR kits for use in cases where serology does not provide conclusive results, or in the follow-up of patients undergoing specific treatment. The current situation contrasts with the early diagnosis of the disease, when there was only one serological test, which was only performed in research services.

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Continental problem

Chagas disease as a problem of the American Continent

João Carlos Pinto Dias 

Centro de Pesquisas René Rachou/Fiocruz

E-mail: jcpdias@cpqrr.fiocruz.br 

This theme has two main strands, according to the angle of approach: the first referring to the eco-biological and historical origins of American trypanosomiasis and the second to aspects of its social impact and its control in the region. From one angle are the bio-ecological factors that determined the occurrence of the early cycles of Trypanosoma cruzi and, on the other, the entire political, social and economic context that caused the spread of the endemic and particularized the affected populations, also determining the prospects for control. A third angle focuses on and shows the importance of Latin American scientific production on the subject, as well as the political and social role of researchers in coping with the disease.

Several studies, since Carlos Chagas, have already located the almost exclusive distribution of the disease in New World lands, initially based on surveys of domiciled vectors and their degree of natural infection by T. cruzi, gradually complemented by data from human disease (initially acute cases) and also by the detection of Chagas-infected domestic and wild reservoirs in 1911 and 1932, Mazza in 1949, Dias in 1953, Freitas in 1960, Dias and Coura in 1997, and reported by WHO in 2002. In the original description Carlos Chagas already defined an American entity because it recognized that it was a new trypanosomiasis that he had discovered in America, different from the African one. In addition to T. minasense, also discovered by Chagas, a number of other trypanosomatids would be described on the continent, with prominence the group vespertilionis (bats) and especially T. rangeli, also carried by triatomines, but not pathogenic for the man. With the findings of natural infections of humans by T. cruzi, triatomines and wild and domestic reservoirs from the southern United States to Patagonia, the “American” denomination for trypanosomiasis cruzi was never disputed, as revised by Dias in 1953, Coura in 1997 and Romero Sá in 2006.

The natural transmission of T. cruzi has been occurring in the American continent for several millennia from a wild cycle much older than the domestic one. The latest evidence of human infection dates back to a much more recent time, detected in Peruvian and Chilean mummies of about two thousand years BC. The spread of the endemic occurred mainly after the discovery of Columbus, originating from large population movements, reaching the peaks of endemicity in the first half of the twentieth century, as described by Dias and Coura in 1997 and reported by WHO in 2002. Modern Molecular Biology and Genetics studies indicate the evolution of T. cruzi from common ancestors with Australian trypanosomatids, existing prior to the separation of Pangea, the cruzi being restricted to the Americas and being transmitted by hematophagous hemiptera of the Triatominae subfamily, whose almost all known species have been limited to the New World, as reviewed by Schofield in 1994 and Zingales et al. in 1999. Human infection basically depended on man’s approach to the triatomines, corresponding to the process of domiciliation (colonization of artificial ecotopes) of the latter, which occurred for a few species throughout Latin America, as reviewed by Martins in 1968, Barretto in 1979, Forattini 1980 and Dias and Coura in 1997. In the last decades, indigenous cases of human Chagas disease have been detected in other continents, due to the migration of infected people that enable congenital transfusion transmission, organ transplants and laboratory accidents, as revised by Dias & Coura in 1997 and reported by WHO in 2002.

From an epidemiological and political point of view, Chagas disease is basically a problem in Latin America, more specifically in its continental countries. There are an estimated 12-14 million T. cruzi-infected individuals in 19 American countries of Iberian colonization, with only sporadic cases of natural transmission occurring in the United States. A proportion of between 10% and 40% among those infected, those who already have or will have chronic heart disease due to American trypanosomiasis, and of which at least 10% will have a severe form that is likely to cause deat. and loss of precious years of productive life, as shown by Dias & Coura 1997, Akhavan in 1998 and WHO in 2002. In addition to heart disease, digestive forms (predominant in South America), absenteeism, social security and hospital costs, lawsuits, perpetuation of family poverty in endemic areas, low productivity and the costs of control and surveillance programs (including blood banks) are important indicators of the financial and social costs of countries affected by the disease. In addition, the increasing chagasic migration to the United States (far more than to Canada) is creating a major concern in the United States about the natural risks of transfusion, congenital and organ transplantation, entailing expenses with the management of chronic patients, especially those with heart disease, as reviewed by Schmunis in 1997 and reported by WHO in 2002. From the early enzootic cycle, human disease spread throughout the Americas due to circumstances and factors of a basically anthropic and social political nature depicted in poor quality rural ranches, socially excluded populations, pockets of poverty and low production, inefficient health systems and geographically open spaces, mainly due to intensive deforestation. In this context, the domiciled triatomine will be marked by geo-ecological factors such as high salinity levels, very dense umbrageous spaces, varied hygrometric indices, high altitudes and latitudes beyond the 49º parallel. S., as revised by Forattini, Schofield, Carcavallo et al., Dias and Coura in 1997 and reported by WHO in 2002. In northern North America, along with the latitude and absence of highly domiciliary triatomines, are on the scene socio-economic and political factors such as the type of human colonization of the United States and Canada that will not give rise to crude housing such as “cafuas”, nor the social exclusion of the Latin region, as pointed out by Briceño-León and Dias and Borges Dias.

Located in the poorest part of the New World, this trypanosomiasis will not have the repercussion or motivation to study as other more universal protozooses, such as malaria and leishmaniasis. It is basically a problem of the region, due to its incidence, distribution and social medical impact, naturally generating greater interest and expertise in the Latin American segment starting with its discovery. Chagas disease is not an obstacle to the process of occupation of spaces by foreign powers, given its slow clinical evolution and the recent time of its epidemic peaks, occurring mainly in the twentieth century, when the affected countries were already politically independent. For this reason, Carlos Chagas, in 1911, called for the governments of the affected countries themselves to undertake the relentless struggle against the Conorhinus, linking this struggle to the development of nations, the occupation of land and the improvement of the race. Three decades after this position, disciples of Chagas resumed the motto, mainly as a consequence of the well-known events of Mendoza (IX Meeting of MEPRA and description of Romaña) and the works of Bambuí, that culminated with the systematization of epidemiological studies and the definitive characterization of the chronic chagasic heart disease, as reviewed by Coura in 1997 and Dias and Schofield. Emmanuel Dias, Cecilio Romaña, Salvador Mazza, Pedreira de Freitas and Francisco Laranja who will pioneer the idea that the disease was a continental problem and from this, flowed unequivocal governmental responsibilities of endemic countries, reviewed by Dias in 1988. In this context, two fundamental situations intersected: on the one hand, the scientific evolution of Latin American “chagologists” (including the development of disease-prone tools and strategies such as serology and electrocardiography) and on the other the involvement of the Pan American Health Organization (PAHO), assuming a catalytic and motivating role with regional governments and the scientific community, as discussed by Dias and Schofield. In general, both situations occurred from the second half of the 1950s onwards, thanks to very particular efforts researchers and health workers involved in the disease, already described the main clinical conditions and forms of transmission, as well as basic prospecting and control tools (vector and transfusion). Although prevalence surveys were expanding in a relatively short time in various parts of the Continent, morbidity and mortality studies, which are still very scarce in many countries, have lagged behind, which has significantly slowed down control in many countries, such as reviewed by Coura in 1997 and Dias & Schofield. In a more incisive way, Emmanuel Dias was responsible for the important instigating role of studies and actions to control the disease on the continent, not only mapping it in an exemplary way already in the 1950s, but also stimulating regional studies, developing work strategies, forming followers and stimulating several countries and PAHO itself. This journey was accompanied by formidable partners such as Pedreira de Freitas, Mário Pinotti, Félix Pífano, Amador Neghme, Cecílio Romaña, Arnoldo Gabaldón, Hugo Escomel, Rafael Torrico, Rodrigo Zeledón and many others, as reported by Dias in 1947 and 1988. The growth of publications, control experiments, and surveys on the disease became logarithmic in the late 1950s, at a time that coincided with a strong sanitary effervescence in the fight against malaria in the region. It is emblematic of a collection by Dias to the health authorities and particularly to PAHO, in 1958, when he vehemently denounced their neglect of Chagas disease at the International Congress of Malariology and Tropical Diseases in Lisbon, described by Dias in 1959. This situation began to change, especially with PAHO’s greater involvement in the fight against the disease and the closer approach among the scientists involved, as described by Romaña in 1979 and Dias and Schofield. Particular role will play regional instances and programs such as CNPq’s Integrated Endemic Disease Program (Brazil), Human Health Program (Argentina), Brazilian Society of Tropical Medicine and Tropical Disease Research (WHO/UNDP, WB). In the 1980s, some national vector control programs were matured and the definitive control of blood banks was demarcated with the advent of human immunodeficiency syndrome (AIDS). In the following decade there was coalition and greater cooperation between several countries in the region, with the International Initiatives to fight the disease, a foreshadowing of new times and substantial advances in the transmission of T. cruzi in Latin America, as reported by Coura in 1997 and Dias in 1988 and reported by the WHO in 2002.

At the continent’s most contextual level, the recognition and management of the disease goes through complex political issues, starting with the fragmentation of social and international policies, for decades the region has been dependent on foreign aid and lacking in ethical and democratic values, as described by Dias & Borges Dias, Briceño-León and Coura. In fact, the great problem of human Chagas disease was its enormous regional expansion, dependent on spurious relations of production and the consequent political and social exclusion of the affected populations, situations of difficult, slow and complex solution, as proposed by Martins in 1968. and Dias and collaborators in 1994. In counterpoint, Chagas disease has unequivocally contributed to the improvement and maturity of the Latin American scientific community, which has the greatest expertise on the endemic and the propellant engaged in its control. It has also served as a motivator for important medical and social analyzes in the region, denoting and helping to understand political and social problems and causal factors involved in the production, expansion and control of the endemic. Positively, since the 1990s, disease control in the region has assumed a form of cooperation and integration among countries, in the midst of so-called successful “initiatives” such as the Cone Sul, the Andean Pact, Central America, the Mexico and the Amazon, thus contributing to the consolidation of regional identity, as reviewed by Dias and collaborators in 1994, Schmunis in 1997 and reported by WHO in 2002.

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PIDE

The Integrated Program for Research in Endemic Diseases (Pide/CNPq) and research on Chagas disease in the 1970s and 1980s

Nara Margareth Silva Azevedo

Casa de Oswaldo Cruz/Fiocruz

E-mail: nazevedo@fiocruz.br

Simone Petraglia Kropf

Casa de Oswaldo Cruz/Fiocruz

Email: simonek@coc.fiocruz.br

José Rodrigues Coura

Instituto Oswaldo Cruz/Fiocruz

E-mail: coura@ioc.fiocruz.br

The scientific and technological policy implemented in Brazil in the 1970s was decisive for the institutionalization of the scientific community dedicated to the study of Chagas disease. The link between the military’s conception of economic development and the promotion of science and technology (S&T) dates back to the international conjuncture created with the end of World War II. In the Brazilian case, it was expressed at the founding, in 1951, of the National Research Council (CNPq), as a result of military interests around the association between national security and nuclear energy.

CNPq’s role as a planning body for the field of S&T began with a major overhaul that underwent in 1964, when it ceased to be an institution primarily devoted to the concession of scholarships and regular research grants, but also as a consulting of the Brazilian Academy of Science (ABC), the actions of formulation and programming of scientific and technological policy as a whole.

This guideline deepened with the creation in 1972 of the National System of Scientific and Technological Development (SNDCT), which, through the resources of the National Fund for Scientific and Technological Development (FNDCT, created in 1967) and the Basic Plans of Scientific and Technological Development (whose first edition was for the period 1973/4), materialized the axis of government planning policy for the area. This policy also had, as other important milestones of the period, the formalization of the national postgraduate system (instituted in 1965 and which would lead to the I National Postgraduate Plan in 1975) and the university reform of 1968, aiming to decentralize the academic structure (by replacing chairs with departments) and stimulating the development and diversification of scientific research at the university.

CNPq was the central coordinating body of the SNDCT. In late 1974, it became a private law foundation, formally linked to the Planning Secretariat (Seplan) and endowed with administrative and financial autonomy. Moving its headquarters to Brasilia, it was renamed the National Council for Scientific and Technological Development, and its duties were substantially expanded to include not only the normal care of the scientific community, but also the coordination of various integrated multidisciplinary programs. regional or sectoral interest.

The Integrated Program for Endemic Diseases (Pide) was one of these programs, and was an example of the effects of the S&T policy implemented in the 1970s, as well as the role that scientists played as protagonists in its development.

The first meeting to discuss the idea of a targeted action in support of endemic disease research took place in June 1972 at ABC’s headquarters in Rio de Janeiro. The following researchers were present: Aluizio Prata, from the Faculty of Health Sciences from the Federal University of Bahia, José Rodrigues Coura and Antonio de Oliveira Lima, from the Faculty of Medicine from the Federal University of Rio de Janeiro, Naftale Katz, from the Oswaldo Cruz Foundation, Benjamin Gilbert of the Navy Research Institute and Fernando Pires of the National Museum of Rio de Janeiro. Also in attendance were the head of the CNPq Scientific Technical Department, Manoel da Frota Moreira, the head of the CNPq Biomedical Sciences Sector, Firmino de Castro, the representative of FNDCT/Finep, José Walter Bautista Vidal, and two representatives of Funtec/BNDE, Amilcar Ferreira Ferrari and Hélio França.

The group prepared the document Schistosomiasis: foundations for a National Research Plan and decided that the program should be implemented by CNPq. Six months later, the same participants met again to discuss questions concerning Chagas disease research and wrote another document, similar to the first, called the Integrated Chagas Disease Research Plan.

In April 1973, the CNPq President Arthur Mascarenhas forwarded both documents to Seplan, requesting funding. Two months later, it was approved that Finep would transfer funds from the FNDCT to the Council to initiate the Integrated Plan for Research on Schistosomiasis and Chagas Disease, subordinated to the CNPq Scientific Technical Department. The group formed for the scientific coordination of the program in its initial phase (1973-1974) was composed of almost all of those present at the ABC meeting (Antonio de Oliveira Lima, Aluizio Prata, Wladimir Lobato Paraense, Benjamin Gilbert and José Rodrigues Coura, Manoel Frota Moreira and Firmino Torres de Castro) and approved the first projects in September, nine of them in schistosomiasis and thirteen in Chagas disease.

From 1975 onwards, due to the demand of the researchers themselves linked to the study of endemic diseases, projects on leishmaniasis and malaria began to be accepted and the program was renamed PIDE. A new group was then assigned to the scientific coordination of the program, composed by researchers Aluizio Prata (coordinator), Antonio de Oliveira Lima, Benjamin Gilbert, Firmino de Castro, Guilherme Rodrigues da Silva, José Rodrigues Coura, Marcello de Vasconcellos Coelho, Wladimir Lobato Paraense and Zigman Brener. This group would remain the same until 1985 (except for the replacement of Lobato Paraense by Amaury Domingues Coutinho in 1980).

The expectation of Finep, the funding agency, was that PIDE would articulate the production of scientific knowledge with the perspective of social application, providing concrete solutions to problems related to research and control of endemics in the country.

Those responsible for the scientific coordination of PIDE, while emphasizing the social importance of the program, sought to ensure the widest possible scope for stimulating research, with regard to both its basic and applied aspects. Without establishing priority or strategic lines of action, the coordinating group, formed by researchers recognized in the academic community, had full autonomy to approve the aid, using as a fundamental criterion the scientific quality of the projects. In the testimonies of scientists included in this group, it is recurrent to emphasize that the combination of free demand with the peer-based and merit-based judgment system was one of the main factors responsible for the success of the program. In the words of Zigman Brener, “the basic philosophy was to create or expand knowledge in the area of ​​endemic diseases. Thus, any project that had scientific merit, whether in the basic or applied area, and which contributed to increasing scientific knowledge, was accepted, ”as quoted in Mello 1987.

Besides being in charge of the projects´ approval, it was up to the scientific coordination of PIDE to negotiate with Finep the transfer of resources from the FNDCT and to establish its allocation in the accepted projects.

Over the six program bienniums (between 1973 and 1986), a total of 971 projects were funded, and the number of grants grew significantly over the period. The vast majority (499 projects) concerned research on Chagas disease. The areas of knowledge with the largest number of projects funded by PIDE were immunology (243), epidemiology (190), parasitology (139) and pathology (133).

Although the orientation expressed by the scientific coordination would be to fund the production of knowledge on endemic diseases regardless of the basic or applied nature of the research, the overall results of the program point to a trend towards demand and care more focused on basic research. Considering that until 1984 PIDE supported practically all the submitted projects, it can be said that this trend expresses the type of demand at that time, expressing the great interest of researchers of the basic areas in relation to studies on endemic diseases in the country.

One of the factors that explain this movement was the intense renewal experienced by disciplines such as immunology and biochemistry, under the impact of the scientific-technological revolution derived from the diffusion of new genetic engineering techniques. The prospect of employing such methodologies through the use of parasites as models for investigating basic biological problems, coupled with the ease of resources offered by PIDE, has made research on parasitic diseases a field of interest to many immunologists, biochemists and molecular biologists, many of them recently graduated, according to new international trends in the biological sciences.

This movement was particularly expressed in PIDE’s support for numerous projects in the basic area of Chagas disease (which contributed to diversifying research groups and lines of research on the topic): “T. cruzi is an excellent model for the study of eukaryotic cell biology, being used to understand biological processes of great importance, such as the mitochondrial DNA gene expression (the mitochondrial DNA in trypanosomatids is concentrated in a typical organelle of these microorganisms, the kinetoplast) and cell differentiation (little known biological phenomenon occurring during the T. cruzi evolutionary cycle)

The attraction of researchers from other disciplines and the incorporation, in the field of parasitic studies, of modern techniques and approaches of investigation have generated, in turn, a movement of uplift and renewal of parasitology itself, a discipline of long tradition in Brazil but which, according to the evaluation of the CNPq in 1978, suffered, until the advent of PIDE, a gradual process of stagnation and emptying, due precisely to the methodological gap with internationally applicable research guidelines. The impact of the program on the resumption of the dynamism of parasitology, which began to assume a multidisciplinary character in accordance with the new international standards of knowledge production, was thus pointed out in an evaluation of the CNPq published in 1982:

“Not only has global scientific activity increased, as measured in terms of published works, but it has also improved its quality, which can be inferred from the growing number of national works in international journals. In addition, the absolute number of researchers involved in basic research, subsidized by PIDE, increased considerably between 1973 and 1981.”

Another key aspect of PIDE, in its broader scope, was its role in training qualified human resources for biomedical research. Created shortly before Capes’ launch of the National Post-Graduation Plan, the program allocated resources to various researches developed in master’s and doctorate courses in several Brazilian universities. The overall analysis of health S&T performance in 1975/79 revealed that PIDE was the main vehicle for research funding at universities in related areas.

As the program coordinators affirm, the main factor of PIDE’s success and effectiveness was the autonomy granted to this group of scientists in its management:

“The participation of the CNPq bureaucracy was minimal, limited to the release of resources in accordance with the opinions of the coordinating group, the collection of individual reports and rendering of accounts and the submission to FINEP of the rendering of accounts consolidated by the financial body of the council and the overall technical reports prepared by the coordinating group. (…) It is possible to state that, strictly speaking, the PIDE was managed by the scientific community itself”.

This situation prevailed until 1984, when PIDE underwent a restructuring that would substantially alter its format and operation. In the context of the fiscal crisis of the Brazilian State since the early 1980s, budget constraints for the S&T area imposed new conditions for financing the sector and generated a reorientation in the scientific and technological policy itself, which began to favor the areas of greater technological applicability.

This scenario had an impact on PIDE’s financing mechanisms, with Seplan’s decision to suspend, from 1982, the transfer of funds that Finep allocated to the program. The funds began to be negotiated year by year, with part of it coming from CNPq’s own budget and part from the General Union Charges, via Seplan, which made it much more difficult to meet the demand presented to the program, as it had been done so far.

Based on guidelines from the CNPq Scientific and Technological Council (CCT), in the mid-1980s, the dynamics of PIDE’s coordination were restructured, through the renewal of its researchers and the division of their attributions between two work groups of researchers: an Advisory Committee, composed of the coordinating scientists of the PIDE’s thematic areas of activity, with a non-renewable two-year term, and an Advisory Group, made up of representatives of the funding institutions, scientific associations and societies, the service institutions of the Ministry of Health directly related to the theme of endemics and the Program Advisory Committee itself. Notwithstanding such reformulation, the Program ended in 1987.

The effects of PIDE on Chagas disease research were decisive, due to it a significant expansion and strengthening of the disciplinary and institutional boundaries of the scientific community in the area. According to data collected by Aluízio Prata, in just five years of existence of the program, i.e. between 1974 and 1979, the number of published works increased by 37.7%, from 726 to over 1000.

One of the initiatives of PIDE was the publication, under the coordination of Aluízio Prata, of the National Bibliography of Chagas Disease, covering the period 1909 and 1979, and also a collection of the main scientific works of Carlos Chagas.

In addition, the program was the basis from which the Annual Chagas Disease Basic Research Meeting was organized from 1974 onwards, which became a fundamental space for articulation and representation of the scientific community linked to the theme, to which would be added the Annual Meeting of Applied Research on the theme, instituted in 1984. The celebrated meetings of Caxambu and Uberaba, which continue to this day, represented the institutionalization of political-academic forums that would design such a field of research nationally and also internationally.

Another significant consequence of the institutionalization process driven by PIDE was the significant participation of Brazilian researchers linked to the Chagas theme in Tropical Disease Research (TDR), a program organized by the World Health Organization in 1975 and which would have great repercussion and important implications for the research in parasitic diseases at international level.

PIDE also played a fundamental role from the point of view of practical actions in the face of Chagas endemic disease. In addition to inducing research related to the control of transfusion transmission of the disease, the program was a decisive factor for conducting the first major national sero-entomological survey conducted by the Ministry of Health between 1975 and 1980, which generated accurate information on the prevalence of chagasic infection and on the geographical distribution of triatomines in the country and, thus, making possible the implementation of the National Control Program in the 1980s.

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WHO

The World Health Organization and Chagas disease

Fabio Zicker

World Health Organization, Geneva, Suiça

E-mail: zickerf@who.int

The World Health Organization (WHO) and the Pan American Health Organization (PAHO) have been supporting endemic countries by mobilizing political, scientific, technical and economic resources to control Chagas disease. Historically, PAHO has contributed by articulating effective policies and coordinating actions to support the elimination of vector and blood transfusion transmission. Both organizations have supported opportunity creators and decision makers alike to understand the issues involved and the knowledge still needed for effective action, bringing scientific knowledge to control activities, establishing norms and standard procedures, consolidating information, developing instruments, funding and monitoring the implementation of actions.

Scientific support and technical cooperation, side by side, from WHO and PAHO have greatly contributed to estimating the magnitude and distribution of Chagas disease, identifying factors associated with its transmission and continuity. PAHO’s participation has been critical in the success of the Southern Cone Initiative (INCOSUR) and in the mobilization necessary to launch the Andean, Amazonian and Central American Countries Initiative, as described by Moncayo in 2003. The Program for Research and Training in Diseases UNICEF/UNDP/World Bank/WHO Tropical Committees have united the scientific community and Chagas disease control initiatives by reviewing the scientific evidence on the disease, setting trends, leading and setting the research agenda.

TDR has supported relevant research not only through technological innovation applied to knowledge of the pathogenesis and genetic bases of the disease, but also by supporting the development of instruments and operational research related to vector control, as presented by Morel in 2000. Several methodologies aiming at the standardization of clinical, epidemiological, laboratory and entomological observations were developed and validated through studies involving several countries. New intervention instruments such as insecticide bottles and paints and intervention and follow-up methodologies directed and specific to the community were developed. In parallel, most of the investments were focused on the development of human resources for research, infrastructure and technology transfer, particularly in the genomics area. Since its inception, TDR has invested $15 million directly in research and training in Chagas disease research. This investment influenced the contribution of other entities from different parts of the world.

Some key examples of historical facts, objectives and scientific successes related to standardization and the political role of WHO, PAHO and TDR support for research and development in Chagas disease are presented below:

• “WHO and PAHO Technical Cooperation on Policy and Implementation –

Historical facts and reference documents” (link)

• “TDR/WHO and PAHO Technical Cooperation on Research and Development: Historical scientific milestones”(link)

• “Current Chagas disease research priorities (as per TDR’s WHO Scientific Working Group on Chagas disease, 2005)” (link)

• References (link)

Technical Cooperation on Policy and Implementation between WHO and PAHO

Historical facts and reference documents

• 1942 – The XI Pan American Sanitary Conference, Washington, USA, recommended that all governments on the American continent carry out studies related to Chagas disease and its medical and social aspects and to provide solutions for rural housing problems (CSP11.R14) .
• 1943 – The Oswaldo Cruz Institute Research Center was created in Bambuí.
• 1947 – The XI Pan-American Sanitary Conference, Washington, USA, recommended carrying out an epidemiological survey of Chagas disease in all countries of the Western Hemisphere; that studies be carried out on the biology of Schisotrypanum cruzi, on triatomines and the improvement of diagnostic methods; that studies be carried out in order to develop new types of rural housing with minimum standards of health for rural populations; that systematic studies of insecticides were carried out in campaigns against triatomines (CSP12.R11).
• 1960 – The Chagas Disease Study Group meeting, March 7-11, Washington, USA, led by Dr. Horwitz, director of PAHO, aimed to review aspects of public health related to control. The importance of research in support of control activities and inter-country coordination was highlighted (WHO, 1960).
• 1977 – First Meeting of Scientific Groups Working on Chagas Disease, November 14-18, Buenos Aires, Argentina. This meeting formulated the research priorities of the TDR/WHO Chagas Disease Program (Doc. TDR/CHA-SWG (1)/77.3.
• 1977-1985 – The study “Control of Chagas disease through the Improvement of Rural Housing – “Trujillo”, from Venezuela, supported by PAHO, showed the correlation between poor housing and infestation by the vector. A model of community participation in housing improvement was successfully developed.
• 1979 – Workshop on Recommendations for Multidisciplinary Research in the Epidemiology of Chagas Disease, 16-19 July, Brasilia, Brazil. This meeting of specialists formulated the standard protocol for the development of studies on the prevalence of human infection and infestation of housing in order to estimate the number of cases of Chagas disease in the American continent (Doc. TDR/EPICHA/79.1/Rev.1 ).
• 1986 – Feasibility of Analytical Epidemiological Studies in Chagas Disease: Recommendations for a standardized protocol. February 28th to March 2nd, Belo Horizonte, Minas Gerais, Brazil. Meeting organized by TDR to establish a standardized protocol for population-based studies. This protocol was the basis of several longitudinal studies on the morbidity and mortality of Chagas disease in Latin America (Doc. TDR/CHA/EPD/PROTO/86.3 7p).
• 1987 – Necessary Research in the area of Control of Chagas Disease Vectors. September 28-Oct 2, Panama. WHO meeting to define vector control priorities (Doc. TDR/CHA/PAN/87.3 12p).
• 1990 – The 43rd World Health Assembly passed resolution – WHA 43.18 on 17 May – calling for partnerships of bilateral and multilateral agencies, pharmaceutical industry and research institutions to direct efforts towards research and control of tropical diseases, including Chagas disease, in endemic countries. The resolution endorsed TDR’s priorities, including the implementation of the new Vector Control Method for Chagas disease, and asked the Director General to confirm the Special Program’s continued leadership role in global tropical disease research, strengthening collaboration, promoting the commitment of endemic countries to research and the mobilization of additional contributions.
• 1991 – The report of the WHO Expert Committee provides the consolidation of knowledge on the biology, epidemiology, prevention and control of Chagas disease and recommendations for research (WHO, 1991).
• 1991 – First Meeting of the Intergovernmental Commission for the Elimination of Triatoma infestans and the Interruption of Transfusion Transmission of American Trypanosomiasis. Buenos Aires, Argentina. The meeting was organized by PAHO and established the Initiative’s guidelines (Doc. PAHO/PNSP/92.18).

• 1992 – Launch of the Southern Cone Initiative – INCOSUL to control/eliminate Chagas disease involving Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay. Concrete plans for technical cooperation between countries and international missions to monitor results and evaluate programs have been finalized (PAHO 2002, PAHO/WHO 1993).

• 1993 – Indicators for Elimination Certification of Triatoma infestans, Uberaba, Minas Gerais, Brazil. The Meeting established measurable parameters and methodologies to be used to certify vector elimination in the Southern Cone Initiative.
• 1997 – Launch of the Andean Countries Initiative for vector and transfusion control of Chagas disease – IPA, involving Colombia, Ecuador, Peru and Venezuela. (WHO/TDR 1998).
• 1997 – Launch of the Initiative of Central American countries to interrupt vectorial and transfusion transmission of Chagas disease – INPCA, involving El Salvador, Guatemala, Honduras, Mexico, Nicaragua, Panama (WHO/TDR 1998).
• 1997-1998 – WHO reports progress towards Interruption of Chagas disease transmission through vector elimination. An investment of over $200 million that resulted in significant reductions in home infestation in Argentina, Brazil, Chile and Uruguay, as reported by Schmunis et al. in 1996 and Moncayo in 1997 and 1999.
• 1997 – A WHO/PAHO Independent Commission certifies Uruguay as an area free of vectorial and transfusion transmission of Chagas disease (WHO 1998).
• 1997 – Cost-Benefit Analysis of the Chagas Disease Control Program. Held in Brasilia by the Ministry of Health, National Health Foundation (FUNASA). The analysis concluded that US$17 was saved in medical care and benefits for every dollar invested in Brazil’s Vector Control Program, as reported by Akhavan in 1998.
• 1998 – The Consultation of PAHO/WHO on treatment of the initial stages of the chronic phase of Chagas disease in children and adults to a group of specialists results in recommendations for the etiological treatment in the acute phase and initial stages of the indeterminate phase of the infection – Report of the Committee of Experts, Washington, USA. (Doc. OPC/HCP/HCT/140/99), PAHO 1999.
• 1998 – Standardization of Electrocardiographic (ECG) Parameters for Epidemiological Studies involving several countries. The study was coordinated by TDR with a view to validating the ECG reading system for chagasic heart disease. Good levels of agreement for intra- and inter-observer readings/interpretations were obtained, as described by Lazzari et al. in 1998.
• 1998 – The 51st World Health Assembly approved the resolution on interrupting the transmission of Chagas disease in Latin America – WHA Resolution 51.14, of 16 May – calling on Member States with populations affected by Chagas disease to determine the extent of the disease, including distribution and vector biology, and to develop action plans to (i) establish inter-country commissions to initiate elimination certification and (ii) coordinate input from the international community. The resolution calls on the general directorate, WHO, to support surveillance plans, via support for the development and implementation of programs to eliminate transmission of Chagas disease by 2010, as well as provide country-by-country certification of elimination.
• 1998 – The potential risk of transfusion-transmitted infection (including Trypanosoma cruzi) was estimated for 10 endemic countries in South and Central America and the Caribbean, based on the index of spread of infectious diseases by blood transfusion. High risk was estimated for Bolivia (with a rate of 1 infection: 43 donations). Data from this analysis in Brazil were not available. A series of scientific articles showed the progressive commitment of endemic countries to improving coverage and procedures for testing donors, as described by Schmunis et al. in 1998 and 2001.
• 1999 – The WHO/PAHO Commission certifies Chile as a free area as an area free of vectorial and transfusion transmission of Chagas disease (Lorca and collaborators in 2001, WHO 2000).
• 2000 – 10 of the 12 endemic states in Brazil (Goiás, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Paraíba, Pernambuco, Piauí, Rio de Janeiro, Rio Grande do Sul and São Paulo) are certified as free areas as areas free of vectorial and transfusion transmission of Chagas disease (WHO 2000).
• 2000 – The WHO Global Collaboration on Chagas Disease Vector Control in Central America summarizes the challenges for Chagas disease vector control in Central America and addresses issues related to the distribution, genetics, biology and control strategies of the main vector ( WHO/CDS/WHOPES/GCDPP/2000.1).
• 2002 – The Second Report of the WHO Committee of Experts consolidates knowledge on the biology, epidemiology, prevention and control of Chagas disease and indicates recommendations for research (WHO 2002).
• 2004 – Launch of the Initiative of the Amazonian Countries for the Surveillance and Prevention of Chagas Disease – AMCHA, aimed at preventing the establishment of vectorial transmission on a large scale in the Amazon region (Bolivia, Brazil, Colombia, Ecuador, French Guiana, Guyana, Peru, Suriname and Venezuela).
• 2005 – Meeting of the Study Group on Chagas Disease, May 17-20, Buenos Aires, Argentina, organized by TDR brought together 66 specialists from 17 countries, addressing diverse disciplinary aspects to (i) review the current situation of the disease, (ii) identify issues relevant to the development of knowledge and (iii) establish the agenda of research priorities. Problems with the sustainability of control activities, expansion and geographic distribution of the disease in the US and Europe, and the need for new drugs were reinforced.
• 2006 – The publication “Disease Control Priorities in Developing countries” (Editors World Bank and Oxford University Press, 2nd Edition) presented the current situation of control, cost-benefit analysis and research needs in Chagas disease (chapter 22 by Remme and collaborators, 2006).
• 2006 – PAHO/WHO declares Brazil free of transmission by the main vector of Chagas disease, Triatoma infestans.

Technical Cooperation in Research and Development between TDR/WHO and PAHO

History of the Main Scientific Events

• 1962 – First Meeting of the Group of Specialists in Research in Chagas disease of PAHO, 4-7 June, Rio de Janeiro, Brazil, to assess the state of knowledge in Chagas disease and to define the most important aspects and methodologies to consider and review ongoing studies. Report of the Group of Specialists in Research on Chagas Disease – RES 1/15: 17p.
• 1963 – Research Opportunities in Chemotherapy for Chagas disease in the Americas. PAHO Scientific Meeting in response to recommendations in WHO Technical Report Series No. 202 and 1992 Expert Group Meeting to review and coordinate testing of new compounds (RES 2/21).
• 1975 – PAHO International Symposium on New Approaches in American Trypanosomiasis Research – 18-21 March, Belo Horizonte, Minas Gerais, Brazil. A publication with contributions from 77 participants from 9 endemic countries reviewed current knowledge and research on Chagas disease (PAHO 1975).
• 1980 – 1985 – TDR-funded Epidemiological Cross-Section Studies using standardized protocols in 9 countries with deficient information on infection prevalence and vector infestation (Chile, Colombia, Ecuador, Honduras, Nicaragua, Panama, Paraguay, Peru and Uruguay).
• 1980 – 1985 – Standardization of Serological Techniques and Diagnostic Criteria for human infection by Trypanosoma cruzi and Chagas disease and creation of the Continental Network of Laboratories in 14 endemic countries, as reported by Camargo and collaborators in 1986.
• 1983 – 1990 – Several prospective longitudinal studies on the course of human infection and clinical pathology were conducted during this period in several Latin American countries, as reviewed by Apt et al. in 1983, Coura et al. in 1983, Pereira et al. in 1985, Maguire and collaborators in 1987 and Mota and collaborators in 1990.
• 1986 – Cloning of the Trypanosoma cruzi genome, as described by Peterson et al. in 1996.
• 1987 – 1990 – Development of defined Trypanosoma cruzi antigens for serological diagnostic techniques for blood bank testing, as reviewed by Moncayo & Luquetti in 1990.
• 1990 – Validation of different Serological Methods for mass testing using blood eluates, as described by Zicker et al. in 1990.
• 1992 – Surveillance Methodology to assess interruption of transmission through serological testing of students is proposed, as described by de Andrade et al. in 1992.
• 1992 – 1995 – Development, field testing and industrial production of slow-release insecticide formulations: insecticide paints in Brazil and Argentina, as described by Oliveira Filho in 1995.
• 1992 – Development and industrial production of paints, fumigators, flasks and sensor boxes in Argentina and Brazil.
• 1994 – Launch of the Trypanosoma cruzi Genome Project with support from TDR and implementation by Research Groups in Europe, South America and the USA, as reviewed by Zingales in 1997.
• 1996 – Publication of the first double-blind clinical trial with a Benznidazole test for the treatment of children in the indeterminate phase, showing an efficacy of 55.8% based on seroconversion with negative serology. The study led to a recommendation by PAHO (Doc.OPC/HCP/HCT/140/99) for the treatment of children, which was adopted as policy in several countries, as reviewed by de Andrade et al. in 1996.
• 2001 – Validation of recombinant Trypanosoma cruzi antigens for serological tests, as described by da Silveira and collaborators in 2001.
• 2002 – Publication of “Strategic emphases for Tropical Disease Research” by TDR. A matrix of disease research priorities, including Chagas disease, and proposed functional areas, as described by Remme et al. in 2002.
• 2002 – Transfer of management and funding of the Task Force on Operational Research in Chagas disease from TDR/WHO in Geneva to PAHO in Washington, aiming at closer support to endemic countries and control programs.
• 2005 – Initiative of the “BENEFIT Trial”, a multi-center double-blind study to evaluate Benznidazole for the treatment of chronic Chagas disease. This will be the first study to use the endpoints “death and serious cardiovascular events” to assess treatment efficacy as described.
• 2006 – An International Commission (PAHO/WHO) declares Brazil free of transmission by the main vector of Chagas disease, Triatoma infestans.

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